Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer

NCT05231122 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: I 1277721NCI-2021-13609HT9425-23-1-1063
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests whether pembrolizumab combined with bevacizumab with or without agonist anti-CD40 CDX-1140 works to shrink tumors in patients with ovarian cancer that has come back (recurrent). Anti-CD40 CDX-1140 works by stimulating certain immune cells within the tumor and, when combined with other immunotherapy treatments, may increase antitumor antibody production. Immunotherapy with monoclonal antibodies, such as pembrolizumab and bevacizumab, may help the body's immune system, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and bevacizumab with anti-CD40 CDX-1140 may decrease symptoms, prolong survival, and improve quality of life in patients with ovarian cancer.

Conditions

Ovarian Clear Cell Adenocarcinoma; Platinum-Sensitive Ovarian Carcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Fallopian Tube Serous Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Clear Cell Adenocarcinoma; Recurrent Ovarian Endometrioid Adenocarcinoma; Recurrent Ovarian Serous Adenocarcinoma; Recurrent Platinum-Resistant Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Primary Peritoneal Endometrioid Adenocarcinoma; Recurrent Primary Peritoneal Serous Adenocarcinoma; Recurrent Primary Peritoneal Clear Cell Adenocarcinoma; Recurrent Fallopian Tube Endometrioid Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Evaluated according to National Cancer Institute Common Terminology Criteria for adverse events (NCI CTCAE) version (v)5.0. Will be summarized by cohort and grade using frequencies and relative frequencies.

  Up to 2 years

• Objective response rate (ORR)

  Will be summarized by cohort (with or without CDX 1140) using frequencies and relative frequencies, with the ORR estimated using 90% confidence intervals obtained by Jeffrey's prior method. The final analysis will be performed on all n=80 (40 in each cohort) evaluable patients; and if the p-value is less than or equal to 0.10, then the triplet regimen will be considered superior with respect to response.

  Up to 2 years

Secondary Outcomes (4)

• Progression free survival (PFS)

  From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years

• Overall survival (OS)

  From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Quality of Life (QoL)EORTC QLQ-C30

  Up to 2 years

Study Arms (2)

Arm I (pembrolizumab, bevacizumab)

ACTIVE COMPARATOR

Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.

Biological: Bevacizumab; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (pembrolizumab, bevacizumab, CDX-1140)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes, bevacizumab IV over 30-90 minutes, and CDX-1140 IV over 90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.

Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140; Biological: Bevacizumab; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, MYL-1402O, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, Zirabev

Arm I (pembrolizumab, bevacizumab); Arm II (pembrolizumab, bevacizumab, CDX-1140)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (pembrolizumab, bevacizumab); Arm II (pembrolizumab, bevacizumab, CDX-1140)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (pembrolizumab, bevacizumab); Arm II (pembrolizumab, bevacizumab, CDX-1140)

Questionnaire Administration OTHER

Ancillary studies

Arm I (pembrolizumab, bevacizumab); Arm II (pembrolizumab, bevacizumab, CDX-1140)

Anti-CD40 Agonist Monoclonal Antibody CDX-1140 BIOLOGICAL

Given IV

Also known as: Agonist CD40 Antibody CDX-1140, Anti-CD40 Agonistic Monoclonal Antibody CDX-1140, CDX 1140, CDX-1140

Arm II (pembrolizumab, bevacizumab, CDX-1140)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years of age.
• Recurrent serous (low grade or high grade), endometrioid, or clear cell recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Participant can be either platinum-sensitive or platinum-resistant, no more than 4 prior lines of treatment, and BRCA status must be known.
• Neoadjuvant + adjuvant is considered one line.
• Participants may have received a prior PARPi, this will not be considered a separate line of therapy if received in maintenance.
• Participants may have received a prior anti-PD1/anti-PDL1 therapy or bevacizumab, these will not be considered a separate line of therapy.
• Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
• Hormonal therapy for OC (e.g. Tamoxifen, aromatase inhibitors etc.) will not count as a separate line of prior therapy.
• Anticipated lifespan greater than 6 months.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patient has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.
• All residual toxicity related to prior anti-cancer therapies (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2 neuropathy from taxanes or platinum and grade 2 hearing loss from platinum) must be resolved to grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.
• Absolute neutrophil count (ANC): \>= 1,500 /mcL.
• Platelets: \>= 100,000 / mcL.
• Hemoglobin: \>= 8 g/dL or 5.0 mmol/L transfusion allowed with adequate bone marrow function

You may not qualify if:

• Primary platinum-refractory patients are excluded
• Has a nonepithelial cancer (germ cell tumors, sex cord-stromal tumors), borderline tumors, mucinous or seromucinous that is predominately mucinous, malignant Brenner's tumor, carcinosarcoma or undifferentiated carcinoma.
• Receipt of any antibody targeting T cell checkpoint or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.
• Has received prior systemic anticancer therapy (including investigational agents or maintenance therapy) within 28 days prior to the planned start of study treatment.
• Hormonal therapy is allowed until the time of randomization
• Progression on prior immune checkpoint blockade therapy.
• Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
• Known or prior malignancy requiring active treatment in the past 2 years. Exception: basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
• Active, untreated central nervous system metastases. Patients with brain metastases identified at screening may be rescreened after the lesion(s) have been appropriately treated; patients with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before administration of study drugs, and treated lesions should demonstrate no new growth on the re-screening scan.
• History of (non-infectious) pneumonitis or has current pneumonitis, including grade 1 (asymptomatic; clinical or diagnostic observations only; intervention not indicated) pneumonitis.
• History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
• Prior therapy with any anti-CD40 antibody.
• Hypersensitivity to bevacizumab, pembrolizumab, or any of its excipients.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator
• Celldex Therapeutics: collaborator
• United States Department of Defense: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Emese Zsiros

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 9, 2022
• Study Start: March 12, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (2)